Several 1-azaindolizine derivatives have been already reported, but the derivatives having oxy and vinyl groups at positions 2 and 3, respectively, are disclosed only in Yakugaku Zasshi, 101, 11, pp. 980-990 (1981), Kurata et al, which has no pharmaceutical data. In recently increasing allergic diseases, rhinitis, bronchial asthma and others, patients are mainly treated with agents, such as disodium chromoglycate (DSCG) or tranilast, which inhibit the release of chemical mediators.
However, these agents do not exhibit sufficient effects against these disease and it is desired to develop a new antiallergic agent having more excellent activity.
Under these circumstances, we, the inventors carried out studies to find that the below-mentioned 1-azaindolizine derivatives of formula (I) exhibits remarkably excellent antiallergic activity, thus completing the present invention.
More specifically, 1-azaindolizine derivatives according to the present invention (hereinafter referred to as compounds of the present invention) are compounds or pharmaceutically acceptable salts thereof represented by formula (I) ##STR1## wherein R.sub.1 and R.sub.2 represent independently hydrogen atom, halogen atom, C.sub.1-4 alkyl group or C.sub.1-4 alkoxy group; and R.sub.3 represents C.sub.1-6 alkyl group, substituted C.sub.1-4 alkyl group (substituent is C.sub.3-5 cycloalkyl group, hydroxyl group, acetylamino group, C.sub.1-4 alkoxy group or cyano group) or C.sub.2-4 alkenyl group.
Synthetic intermediates of the compound (I) according to the present invention (hereinafter referred to as synthetic intermediates of the present invention) are represented by formula (II) ##STR2## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above and R.sub.4 represents C.sub.1-10 alkyl group or benzyl group.
Antiallergic agents of the present invention are agents containing the compound of the present invention as effective component.
The terms used for definition of letters in the formulas (I) and (II) by which the compounds of the present invention and synthetic intermediates thereof are respectively represented are defined and exemplified in the following.
The "halogen atom" may be chlorine, bromine or iodine atom.
The "C.sub.1-4 alkyl group" refers to a straight- or branched-chain alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl or the like.
The "C.sub.1-6 alkyl group" refers to a straight- or branched-chain alkyl group having 1 to 6 carbon atoms such as those referred to in the above-mentioned C.sub.1-4 alkyl group, pentyl, hexyl or the like.
The "C.sub.1-10 alkyl group" refers to a straight- or branched-chain alkyl group having 1 to 10 carbon atoms such as those referred to in the above-mentioned C.sub.1-6 alkyl group, octyl, decyl or the like.
The "C.sub.3-5 cycloalkyl group" refers to a cycloalkyl group having 3 to 5 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl or the like.
The "C.sub.1-4 alkoxy group" refers to a straight- or branched-chain alkoxy group having 1 to 4 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy or the like.
The "C.sub.2-4 alkenyl group" refers to an alkenyl group having 2 to 4 carbon atoms such as vinyl, 1-propenyl, 2-propenyl, 2-butenyl, 3-butenyl or the like.
The compounds of the present invention are for example as follows:
3-(2-Carboxy-2-cyanovinyl)-2-methoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-methoxy-5-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-methoxy-6-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-methoxy-7-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-methoxy-8-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-methoxy-5,7-dimethylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-6,8-dichloro-2-methoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2,8-dimethoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-isopropoxy-2-methoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-ethoxy-8-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-ethoxy-8-isopropoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-methyl-2-propoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isopropoxy-6-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isopropoxy-7-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isopropoxy-8-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-6,8-dichloro-2-isopropoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isopropoxy-8-methoxyimidazo[1,2-a]-pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-ethoxy-2-isopropoxyimidazo[1,2-a]-pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2,8-diisopropoxyimidazo[1,2-a]pyridine and its sodium salt PA0 2-Butoxy-3-(2-carboxy-2-cyanovinyl)-8-methylimidazo[1,2-a]-pyridine and its sodium salt PA0 2-Butoxy-3-(2-carboxy-2-cyanovinyl)-8-isopropoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isobutoxy-5-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isobutoxy-6-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isobutoxy-7-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isobutoxy-8-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-ethoxy-2-isobutoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-isobutoxy-8-isopropoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-methyl-2-sec-butoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-ethoxy-2-sec-butoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-isopropoxy-2-sec-butoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-methyl-2-tert-butoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-isopropoxy-2-tert-butoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-methyl-2-pentyloxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-6,8-dichloro-2-pentyloxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-isopropoxy-2-pentyloxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-carboxy-2-cyanovinyl)-2-hexyloxy-8-methylimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-hexyloxy-8-isopropoxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-methyl-2-vinyloxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-isopropoxy-2-vinyloxyimidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-methyl-2-(2-propenyloxy)imidazo[1,2-a]pyridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-8-isopropoxy-2-(2-propenyloxy)imidazo[1,2-a]pyri dine and its sodium salt PA0 2-(3-Butenyloxy)-3-(2-carboxy-2-cyanovinyl)-8-methylimidazo[1,2-a]pyridine and its sodium salt PA0 2-(3-Butenyloxy)-3-(2-carboxy-2-cyanovinyl)-8-isopropoxyimidazo[1,2-a]pyrid ine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-(3-hydroxypropoxy)-8-methylimidazo[1,2-a]pyrid ine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-(2-hydroxyethoxy)-8-methylimidazo[1,2-a]pyridi ne and its sodium salt PA0 2-(3-Acetylaminopropoxy)-3-(2-carboxy-2-cyanovinyl)-8-methylimidazo[1,2-a]p yridine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-cyclopropylmethoxy-8-methylimidazo[1,2-a]pyrid ine and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-(2-methoxyethoxy)-8-methylimidazo[1,2-a]pyridi ne and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-(2-ethoxyethoxy)-8-methylimidazo[1,2-a]pyridin e and its sodium salt PA0 3-(2-Carboxy-2-cyanovinyl)-2-(3-cyanopropoxy)-8-methylimidazo[1,2-a]pyridin e and its sodium salt PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-2-methoxyimidazo[1,2-a]pyridine PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-2-methoxy-5methylimidazo[1,2-a]pyridine PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-2-methoxy-6-methylimidazo[1,2-a]pyridin e PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-2-methoxy-7-methylimidazo[1,2-a]pyridin e PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-2-methoxy-8-methylimidazo[1,2-a]pyridin e PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-methoxy-5,7-dimethylimidazo[1,2-a] pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-6,8-dichloro-2-methoxyimidazo[1,2-a] pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2,8-dimethoxyimidazo[1,2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-isopropoxy-2-methoxyimidazo[1,2-a] pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-ethoxy-8-methylimidazo[1,2-a]pyrid ine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-ethoxy-8-isopropoxyimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-methyl-2-propoxyimidazo[1,2-a]pyri dine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isopropoxy-6-methylimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isopropoxy-7-methylimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isopropoxy-8-methylimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-6,8-dichloro-2-isopropoxyimidazo[1,2 -a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isopropoxy-8-methoxyimidazo[1,2-a] pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-ethoxy-2-isopropoxyimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2,8-diisopropoxyimidazo[1,2-a]pyridi ne PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-2,8-diisopropoxyimidazo[1,2-a]pyridine PA0 3-[2-Cyano-2-(isopentyloxycarbonyl)vinyl]-2,8-diisopropoxyimidazo[1,2-a]pyr idine PA0 3-[2-Cyano-2-(n-decyloxycarbonyl)vinyl]-2,8-diisopropoxyimidazo[1,2-a]pyrid ine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-butoxy-8-methylimidazo[1,2-a]pyrid ine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-butoxy-8-isopropoxyimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isobutoxy-5-methylimidazo[1,2-a]py ridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isobutoxy-6-methylimidazo[1,2-a]py ridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isobutoxy-7-methylimidazo[1,2-a]py ridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isobutoxy-8-methylimidazo[1,2-a]py ridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-ethoxy-2-isobutoxyimidazo[1,2-a]py ridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-isobutoxy-8-isopropoxyimidazo[1,2- a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-methyl-2-sec-butoxyimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-ethoxy-2-sec-butoxyimidazo[1,2-a]p yridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-isopropoxy-2-sec-butoxyimidazo[1,2 -a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-methyl-2-tert-butoxyimidazo[1,2-a] pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-isopropoxy-2-tert-butoxyimidazo[1, 2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-methyl-2-pentyloxyimidazo[1,2-a]py ridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-6,8-dichloro-2-pentyloxyimidazo[1,2- a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-8-isopropoxy-2-pentyloxyimidazo[1,2- a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-hexyloxy-8-methylimidazo[1,2-a]pyr idine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-hexyloxy-8-isopropoxyimidazo[1,2-a ]pyridine PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-8-methyl-2-vinyloxyimidazo[1,2-a]pyridi ne PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-8-isopropoxy-2-vinyloxyimidazo[1,2-a]py ridine PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-8-methyl-2-(2-propenyloxy)imidazo[1,2-a ]pyridine PA0 3-[2-Cyano-2-(ethoxycarbonyl)vinyl]-8-isopropoxy-2-(2-propenyloxy)imidazo[1 ,2-a]pyridine PA0 2-(3-Butenyloxy)-3-[2-cyano-2-(ethoxycarbonyl)vinyl]-8-methylimidazo[1,2-a] pyridine PA0 2-(3-Butenyloxy)-3-[2-cyano-2-(ethoxycarbonyl)vinyl]-8-isopropoxyimidazo[1, 2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-(2-hydroxyethoxy)-8-methylimidazo[ 1,2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-(3-hydroxypropoxy)-8-methylimidazo [1,2-a]pyridine PA0 2-[3-(Acetylaminopropoxy)-3-[2-(benzyloxycarbonyl)-2-cyanovinyl]-8methylimi dazo[1,2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-cyclopropylmethoxy-8-methylimidazo [1,2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-(2-methoxyethoxy)-8-methylimidazo[ 1,2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-(2-ethoxyethoxy)-8-methylimidazo[1 ,2-a]pyridine PA0 3-[2-(Benzyloxycarbonyl)-2-cyanovinyl]-2-(3-cyanopropoxy)-8-methylimidazo[1 ,2-a]pyridine PA0 Sample 1: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-methoxy-6-methylimidazo[1,2-a]pyridine PA0 Sample 2: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-isopropoxy-8-methylimidazo[1,2-a]pyridine PA0 Sample 3: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-isopropoxy-8-methoxyimidazo[1,2-a]pyridine PA0 Sample 4: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-8-ethoxy-2-isopropoxyimidazo[1,2-a]pyridine PA0 Sample 5: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2,8-diisopropoxyimidazo[1,2-a]pyridine PA0 Sample 6: Sodium salt of 2-butoxy-3-(2-carboxy-2-cyanovinyl)-8-methylimidazo[1,2-a]pyridine PA0 Sample 7: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-isobutoxy-7-methylimidazo[1,2-a]pyridine PA0 Sample 8: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-8-methyl-2-secbutoxyimidazo[1,2-a]pyridine PA0 Sample 9: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-8-ethoxy-2-secbutoxyimidazo[1,2-a]pyridine PA0 Sample 10: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-8-isopropoxy-2-secbutoxyimidazo[1,2-a]pyridine PA0 Sample 11: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-hexyloxy-8-methylimidazo[1,2-a]pyridine PA0 Sample 12: Sodium salt of 2-(3-butenyloxy)-3-(2-carboxy-2-cyanovinyl)-8-methylimidazo[1,2-a]pyridine PA0 Sample 13: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-(3-hydroxypropoxy)-8-methylimidazo[1,2-a]pyri dine PA0 Sample 14: Sodium salt of 2-(3-acetylaminoproxy)-3-(2-carboxy-2-cyanovinyl)-8-methylimidazo[1,2-a]py ridine PA0 Sample 15: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-cyclopropylmethoxy-8-methylimidazo[1,2-a]pyri dine PA0 Sample 16: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-(2-methoxyethoxy)-8-methylimidazo[1,2-a]pyrid ine PA0 Sample 17: Sodium salt of 3-(2-carboxy-2-cyanovinyl)-2-(3-cyanoproxy)-8-methylimidazo[1,2-a]pyridine
Pharmaceutically acceptable salts of the compounds of the present invention may be potassium salt and calcium salt as well as the above-mentioned sodium salt.
Synthetic intermediates of the present invention correspond to C.sub.1-10 alkyl esters or benzyl esters of the compounds of the present invention and may be for example as follows:
The compounds of the present invention can be readily prepared by catalytic hydrogenation or alkaline hydrolysis of the above-mentioned intermediates followed by convertment to the pharmaceutically acceptable salts thereof.
In the case of the catalytic hydrogenation, 10% palladium on carbon, 5% palladium on barium sulfate, platinum oxide may be used as a catalyst; 10% palladium on carbon is preferable. The amount of the catalyst used in the hydrogenation is usually within the range from 0.01% to 0.05% of weight of the intermediates. As for the reaction solvent, methanol, ethanol, acetic acid or dioxane may be used; ethanol is preferable. The reaction temperature may range from 0.degree. to 80.degree. C., preferably within at room temperature. The reaction time may range from 1 to 24 hours which depends on reaction temperature.
In the case of alkaline hydrolysis, alkali used may be potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate. As the reaction solvent, water, methanol, ethanol or their mixture may be used. The reaction temperature may range from 0.degree. to 80.degree. C., preferably from 50.degree. to 70.degree. C., and the reaction time may range from 0.5 to 24 hours, preferably from 0.5 to 2 hours, which depends on reaction temperature.
The compounds (carboxylic acids) obtained by the above-mentioned catalytic hydrogenation or alkaline hydrolysis may be converted to pharmaceutically acceptable salts thereof such as sodium salt, potassium salt or calcium salt in a usual manner; alternatively, said obtained compound may be converted to salts thereof without isolation.
Thus obtained compound of the present invention or pharmaceutically acceptable salts thereof may be isolated by usual separating and purifying manners such as extraction, concentration, neutralization, filtration, recrystallization or column chromatography. The intermediates of the present invention are also novel compounds and are prepared by a similar method described in Chemical & Pharmaceutical Bulletin, 34, 6, 2435.about.2442(1986) Kakei et al and Yakugaku Zasshi, 101, 11, 980.about.990(1981) Kurata et al. More specifically, the intermediate of the present invention is readily prepared as shown in the scheme. Pyridinium bromide of below-mentioned formula (III) is reacted with the compound of below-mentioned formula (IV) in the presence of base such as 1,8-diazabicyclo[5,4,0]-7-undecene, 1,5-diazabicyclo[4,3,0]-5-nonen, sodium ethoxide, sodium methoxide or potassium tert-butoxide and then is reacted to the compound with the formula (V). ##STR3## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined above and X represents halogen.
The synthetic intermediate of the present invention itself has antiallergic activities.
The antiallergic action of the compounds of the present invention obtained by the above-mentioned preparation process was examining by the following inhibition test of homologous passive cutaneous anaphylaxis (PCA) reaction on rats.
Numbers and names of samples used in the test were as follows: